title: Scavenger receptor-BI is a receptor for lipoprotein(a).
abstract: Scavenger receptor class B type I (SR-BI) is a multi-ligand receptor that binds a variety of lipoproteins, including high density lipoprotein (HDL) and low density lipoprotein (LDL), but lipoprotein(a) [Lp(a)] has not been investigated as a possible ligand. Stable cell lines (HEK293 and HeLa) expressing human SR-BI were incubated with protein- or lipid-labeled Lp(a) to investigate SR-BI-dependent Lp(a) cell association. SR-BI expression enhanced the association of both (125)I- and Alexa Fluor-labeled protein from Lp(a). By confocal microscopy, SR-BI was also found to promote the internalization of fluorescent lipids (BODIPY-cholesteryl ester (CE)- and DiI-labeled) from Lp(a), and by immunocytochemistry the cellular internalization of apolipoprotein(a) and apolipoprotein B. When dual-labeled ((3)H-cholesteryl ether,(125)I-protein) Lp(a) was added to cells expressing SR-BI, there was a greater relative increase in lipid uptake over protein, indicating that SR-BI mediates selective lipid uptake from Lp(a). Compared with C57BL/6 control mice, transgenic mice overexpressing human SR-BI in liver were found to have increased plasma clearance of (3)H-CE-Lp(a), whereas mouse scavenger receptor class B type I knockout (Sr-b1-KO) mice had decreased plasma clearance (fractional catabolic rate: 0.63 ± 0.08/day, 1.64 ± 0.62/day, and 4.64 ± 0.40/day for Sr-b1-KO, C57BL/6, and human scavenger receptor class B type I transgenic mice, respectively). We conclude that Lp(a) is a novel ligand for SR-BI and that SR-BI mediates selective uptake of Lp(a)-associated lipids.
authors.affiliation: Cardiology Division, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Amar
authors.forename: Boris
authors.initials: B
authors.lastname: Vaisman
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Bocharov
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Vishnyakova
authors.forename: Lita A
authors.initials: LA
authors.lastname: Freeman
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Kurlander
authors.forename: Amy P
authors.initials: AP
authors.lastname: Patterson
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport
chemical_list: D018955:CD36 Antigens; D017270:Lipoprotein(a)
keywords: apolipoprotein(a); atherosclerosis; lipoprotein receptors; oxidized lipids; selective uptake